CA2444882A1 - Inhibitors of gsk-3 and crystal structures of gsk-3.beta. protein and protein complexes - Google Patents

Info

Publication number

CA2444882A1

CA2444882A1 CA002444882A CA2444882A CA2444882A1 CA 2444882 A1 CA2444882 A1 CA 2444882A1 CA 002444882 A CA002444882 A CA 002444882A CA 2444882 A CA2444882 A CA 2444882A CA 2444882 A1 CA2444882 A1 CA 2444882A1

Authority

CA

Canada

Prior art keywords

compound

phenyl

gsk

pyrazolo

pyridazin

Prior art date

2001-04-30

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108090000623 proteins and genes Proteins 0.000 title claims abstract description 140
• 102000004169 proteins and genes Human genes 0.000 title claims abstract description 139
• 239000013078 crystal Substances 0.000 title claims abstract description 89
• 239000003112 inhibitor Substances 0.000 title abstract description 129
• 102000007474 Multiprotein Complexes Human genes 0.000 title abstract description 12
• 108010085220 Multiprotein Complexes Proteins 0.000 title abstract description 12
• 101150090422 gsk-3 gene Proteins 0.000 title description 4
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims abstract description 571
• 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 claims abstract description 571
• 150000001875 compounds Chemical class 0.000 claims abstract description 189
• 238000000034 method Methods 0.000 claims abstract description 126
• 239000000203 mixture Substances 0.000 claims abstract description 59
• 238000013500 data storage Methods 0.000 claims abstract description 31
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
• 238000013461 design Methods 0.000 claims abstract description 19
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 14
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 9
• 125000000539 amino acid group Chemical group 0.000 claims description 218
• 235000018102 proteins Nutrition 0.000 claims description 147
• 239000000758 substrate Substances 0.000 claims description 114
• 125000003118 aryl group Chemical group 0.000 claims description 67
• 125000004429 atom Chemical group 0.000 claims description 66
• 125000001072 heteroaryl group Chemical group 0.000 claims description 61
• 150000005829 chemical entities Chemical class 0.000 claims description 59
• 125000000623 heterocyclic group Chemical group 0.000 claims description 57
• 125000001931 aliphatic group Chemical group 0.000 claims description 55
• 238000006366 phosphorylation reaction Methods 0.000 claims description 53
• 230000026731 phosphorylation Effects 0.000 claims description 52
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 49
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 46
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 46
• 230000000694 effects Effects 0.000 claims description 36
• 230000002401 inhibitory effect Effects 0.000 claims description 23
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 claims description 22
• 102000001253 Protein Kinase Human genes 0.000 claims description 20
• 108060006633 protein kinase Proteins 0.000 claims description 20
• 230000015572 biosynthetic process Effects 0.000 claims description 19
• 238000003786 synthesis reaction Methods 0.000 claims description 18
• 229920002527 Glycogen Polymers 0.000 claims description 17
• 238000002425 crystallisation Methods 0.000 claims description 17
• 230000008025 crystallization Effects 0.000 claims description 17
• 229940096919 glycogen Drugs 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 239000003981 vehicle Substances 0.000 claims description 15
• 238000002441 X-ray diffraction Methods 0.000 claims description 14
• 239000002671 adjuvant Substances 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 13
• 239000003937 drug carrier Substances 0.000 claims description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 12
• 238000012545 processing Methods 0.000 claims description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 10
• 239000008103 glucose Substances 0.000 claims description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 239000011232 storage material Substances 0.000 claims description 9
• 102000013498 tau Proteins Human genes 0.000 claims description 9
• 108010026424 tau Proteins Proteins 0.000 claims description 9
• 239000012472 biological sample Substances 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 8
• 125000003729 nucleotide group Chemical group 0.000 claims description 8
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
• SEXDCZOTUATPCJ-UHFFFAOYSA-N 5-(3-fluorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC(F)=C1 SEXDCZOTUATPCJ-UHFFFAOYSA-N 0.000 claims description 7
• 239000002773 nucleotide Substances 0.000 claims description 7
• PFHKAGAZRDERTK-UHFFFAOYSA-N 4-(2-anilino-5-methylpyrimidin-4-yl)-n-(2-hydroxy-1-phenylethyl)-1h-pyrrole-2-carboxamide Chemical compound N1=C(C=2C=C(NC=2)C(=O)NC(CO)C=2C=CC=CC=2)C(C)=CN=C1NC1=CC=CC=C1 PFHKAGAZRDERTK-UHFFFAOYSA-N 0.000 claims description 6
• JHXDLIAMKPRADS-UHFFFAOYSA-N 4-(3-fluorophenyl)-5-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC(F)=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 JHXDLIAMKPRADS-UHFFFAOYSA-N 0.000 claims description 6
• 108010046277 H 179 Proteins 0.000 claims description 6
• 210000004369 blood Anatomy 0.000 claims description 6
• 239000008280 blood Substances 0.000 claims description 6
• 230000036765 blood level Effects 0.000 claims description 6
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 239000001226 triphosphate Substances 0.000 claims description 6
• 235000011178 triphosphate Nutrition 0.000 claims description 6
• 230000003936 working memory Effects 0.000 claims description 6
• JWVJFQWLTBIMEV-UHFFFAOYSA-N 4-phenyl-5-pyridin-4-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=NC=C1 JWVJFQWLTBIMEV-UHFFFAOYSA-N 0.000 claims description 5
• JMAGLEWPHWZICN-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=C(F)C=C1 JMAGLEWPHWZICN-UHFFFAOYSA-N 0.000 claims description 5
• 239000000556 agonist Substances 0.000 claims description 5
• 239000005557 antagonist Substances 0.000 claims description 5
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 5
• 239000011549 crystallization solution Substances 0.000 claims description 5
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• NRHHPDMHIVEBSS-UHFFFAOYSA-N n-(1h-indazol-3-yl)-2-[2-(trifluoromethyl)phenyl]quinazolin-4-amine Chemical compound FC(F)(F)C1=CC=CC=C1C1=NC(NC=2C3=CC=CC=C3NN=2)=C(C=CC=C2)C2=N1 NRHHPDMHIVEBSS-UHFFFAOYSA-N 0.000 claims description 5
• LGWDGIALCCNBQU-UHFFFAOYSA-N n-(5-methyl-1h-pyrazol-3-yl)-2-pyridin-4-ylquinazolin-4-amine Chemical compound N1N=C(C)C=C1NC1=NC(C=2C=CN=CC=2)=NC2=CC=CC=C12 LGWDGIALCCNBQU-UHFFFAOYSA-N 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 201000000980 schizophrenia Diseases 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 5
• GSDXVXFWNRXPFN-UHFFFAOYSA-N 4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C12=C(N)NN=C2N=NC=C1C1=CC=CC=C1 GSDXVXFWNRXPFN-UHFFFAOYSA-N 0.000 claims description 4
• 230000002708 enhancing effect Effects 0.000 claims description 4
• 239000004299 sodium benzoate Substances 0.000 claims description 4
• 241000701447 unidentified baculovirus Species 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 3
• 230000006951 hyperphosphorylation Effects 0.000 claims description 3
• 238000002156 mixing Methods 0.000 claims description 3
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 2
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 2
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims description 2
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 2
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims description 2
• VQISKCBTGNMDTP-UHFFFAOYSA-N 4,5-bis(4-fluorophenyl)-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=C(F)C=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=C(F)C=C1 VQISKCBTGNMDTP-UHFFFAOYSA-N 0.000 claims description 2
• NPHKXSDZIKFIRU-UHFFFAOYSA-N 4,5-diphenyl-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C=1C2=C(N)NN=C2N=NC=1C1=CC=CC=C1 NPHKXSDZIKFIRU-UHFFFAOYSA-N 0.000 claims description 2
• FPHUKEUMXVJBDX-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 FPHUKEUMXVJBDX-UHFFFAOYSA-N 0.000 claims description 2
• IVRPJGSBYHTNHT-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=C(F)C=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 IVRPJGSBYHTNHT-UHFFFAOYSA-N 0.000 claims description 2
• OCHNFYUNDYIYRF-UHFFFAOYSA-N 5-(2-chlorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1Cl OCHNFYUNDYIYRF-UHFFFAOYSA-N 0.000 claims description 2
• KJXWMOPZSGTTGD-UHFFFAOYSA-N 5-(2-fluorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1F KJXWMOPZSGTTGD-UHFFFAOYSA-N 0.000 claims description 2
• GQLPYDMYNRVHKC-UHFFFAOYSA-N 5-(2-methylphenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=CC=C1 GQLPYDMYNRVHKC-UHFFFAOYSA-N 0.000 claims description 2
• SJHHGUYUTFSVME-UHFFFAOYSA-N 5-(3-methylphenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=CC=CC=2)=C1 SJHHGUYUTFSVME-UHFFFAOYSA-N 0.000 claims description 2
• SFFFIHJZANPZKT-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=C(Cl)C=C1 SFFFIHJZANPZKT-UHFFFAOYSA-N 0.000 claims description 2
• SUTWDDBXZVUAQG-UHFFFAOYSA-N 5-(4-methylphenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C1=CC(C)=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=CC=C1 SUTWDDBXZVUAQG-UHFFFAOYSA-N 0.000 claims description 2
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
• 229940125773 compound 10 Drugs 0.000 claims description 2
• 229940125797 compound 12 Drugs 0.000 claims description 2
• 229940126543 compound 14 Drugs 0.000 claims description 2
• 229940125758 compound 15 Drugs 0.000 claims description 2
• 229940126142 compound 16 Drugs 0.000 claims description 2
• 229940125782 compound 2 Drugs 0.000 claims description 2
• 229940126214 compound 3 Drugs 0.000 claims description 2
• 229940125898 compound 5 Drugs 0.000 claims description 2
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
• 238000012544 monitoring process Methods 0.000 claims description 2
• 229940124597 therapeutic agent Drugs 0.000 claims description 2
• AKNGRUGMIBUNNX-UHFFFAOYSA-N 3-(3-amino-4-phenyl-2h-pyrazolo[3,4-c]pyridazin-5-yl)benzamide Chemical compound NC(=O)C1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=CC=CC=2)=C1 AKNGRUGMIBUNNX-UHFFFAOYSA-N 0.000 claims 2
• IDFNMLSYDALSTJ-UHFFFAOYSA-N 3-[3-amino-4-(2-methylphenyl)-2h-pyrazolo[3,4-c]pyridazin-5-yl]benzamide Chemical compound CC1=CC=CC=C1C1=C(C=2C=C(C=CC=2)C(N)=O)N=NC2=C1C(N)=NN2 IDFNMLSYDALSTJ-UHFFFAOYSA-N 0.000 claims 2
• JODDKWLYLYBWIZ-UHFFFAOYSA-N 3-[3-amino-5-(3-nitrophenyl)-1h-pyrazolo[3,4-c]pyridazin-4-yl]benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC([N+]([O-])=O)=C1 JODDKWLYLYBWIZ-UHFFFAOYSA-N 0.000 claims 2
• LQJWCMRWFCJIQE-UHFFFAOYSA-N 3-[3-amino-5-(3-phenoxyphenyl)-1h-pyrazolo[3,4-c]pyridazin-4-yl]benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C1=C2C(N)=NNC2=NN=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 LQJWCMRWFCJIQE-UHFFFAOYSA-N 0.000 claims 2
• XBVVEHAQBBQDGO-UHFFFAOYSA-N 4-(2-methylphenyl)-5-(3-nitrophenyl)-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC=C1C1=C(C=2C=C(C=CC=2)[N+]([O-])=O)N=NC2=C1C(N)=NN2 XBVVEHAQBBQDGO-UHFFFAOYSA-N 0.000 claims 2
• XTGMKRNEWFOUIR-UHFFFAOYSA-N 4-(2-methylphenyl)-5-(3-phenoxyphenyl)-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC=C1C1=C(C=2C=C(OC=3C=CC=CC=3)C=CC=2)N=NC2=C1C(N)=NN2 XTGMKRNEWFOUIR-UHFFFAOYSA-N 0.000 claims 2
• LVEJQOZXZPSRLV-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-(3-methylphenyl)-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=CC(Cl)=CC=2)=C1 LVEJQOZXZPSRLV-UHFFFAOYSA-N 0.000 claims 2
• AVDISOMQMOJXHY-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-(3-phenoxyphenyl)-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=C(Cl)C=CC=1C1=C2C(N)=NNC2=NN=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 AVDISOMQMOJXHY-UHFFFAOYSA-N 0.000 claims 2
• FVINWOOTUNSPHX-UHFFFAOYSA-N 4-[3-amino-4-(2-methylphenyl)-1h-pyrazolo[3,4-c]pyridazin-5-yl]benzonitrile Chemical compound CC1=CC=CC=C1C1=C(C=2C=CC(=CC=2)C#N)N=NC2=C1C(N)=NN2 FVINWOOTUNSPHX-UHFFFAOYSA-N 0.000 claims 2
• FNXMBCWYAGWKSG-UHFFFAOYSA-N 4-[3-amino-4-(2-methylphenyl)-2h-pyrazolo[3,4-c]pyridazin-5-yl]benzamide Chemical compound CC1=CC=CC=C1C1=C(C=2C=CC(=CC=2)C(N)=O)N=NC2=C1C(N)=NN2 FNXMBCWYAGWKSG-UHFFFAOYSA-N 0.000 claims 2
• HSVROBQENKSWQY-UHFFFAOYSA-N 4-[3-amino-4-(3-methoxyphenyl)-2h-pyrazolo[3,4-c]pyridazin-5-yl]benzonitrile Chemical compound COC1=CC=CC(C=2C=3C(N)=NNC=3N=NC=2C=2C=CC(=CC=2)C#N)=C1 HSVROBQENKSWQY-UHFFFAOYSA-N 0.000 claims 2
• REFIMIGHWYMMPC-UHFFFAOYSA-N 4-[3-amino-5-(2-chlorophenyl)-1h-pyrazolo[3,4-c]pyridazin-4-yl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1Cl REFIMIGHWYMMPC-UHFFFAOYSA-N 0.000 claims 2
• BCTNHAUKHDCNGB-UHFFFAOYSA-N 5-(1,3-benzodioxol-5-yl)-4-(4-chlorophenyl)-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=12C(N)=NNC2=NN=C(C=2C=C3OCOC3=CC=2)C=1C1=CC=C(Cl)C=C1 BCTNHAUKHDCNGB-UHFFFAOYSA-N 0.000 claims 2
• LLWXDAQULUCWDC-UHFFFAOYSA-N 5-(1,3-benzodioxol-5-yl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=12C(N)=NNC2=NN=C(C=2C=C3OCOC3=CC=2)C=1C1=CC=CC=C1 LLWXDAQULUCWDC-UHFFFAOYSA-N 0.000 claims 2
• YYGUSAHCDWSGJE-UHFFFAOYSA-N 5-(3-chlorophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC(Cl)=C1 YYGUSAHCDWSGJE-UHFFFAOYSA-N 0.000 claims 2
• BNMDZRIGIQLJGI-UHFFFAOYSA-N 5-(3-nitrophenyl)-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC([N+]([O-])=O)=C1 BNMDZRIGIQLJGI-UHFFFAOYSA-N 0.000 claims 2
• YTBPMMBYXWEXTC-UHFFFAOYSA-N 5-(3-phenoxyphenyl)-4-phenyl-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 YTBPMMBYXWEXTC-UHFFFAOYSA-N 0.000 claims 2
• PHHUDUOMJNIKIV-UHFFFAOYSA-N n-(4,5-diphenyl-1h-pyrazolo[3,4-c]pyridazin-3-yl)acetamide Chemical compound C=1C=CC=CC=1C1=C2C(NC(=O)C)=NNC2=NN=C1C1=CC=CC=C1 PHHUDUOMJNIKIV-UHFFFAOYSA-N 0.000 claims 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims 1
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims 1
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims 1
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims 1
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims 1
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 1
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims 1
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims 1
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims 1
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims 1
• OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 claims 1
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims 1
• STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 claims 1
• VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 claims 1
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims 1
• MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims 1
• WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims 1
• FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 claims 1
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 claims 1
• QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 claims 1
• CMDGBRYLFHHLRS-UHFFFAOYSA-N 2-(3-amino-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-5-yl)benzonitrile Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1C#N CMDGBRYLFHHLRS-UHFFFAOYSA-N 0.000 claims 1
• DADYNQDOZIGUGB-UHFFFAOYSA-N 2-(3-amino-5-phenyl-1h-pyrazolo[3,4-c]pyridazin-4-yl)benzonitrile Chemical compound C=1C=CC=C(C#N)C=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 DADYNQDOZIGUGB-UHFFFAOYSA-N 0.000 claims 1
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims 1
• FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims 1
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims 1
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims 1
• NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims 1
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 claims 1
• DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 claims 1
• TXXVFAPDJYIMHK-UHFFFAOYSA-N 3-(3-amino-4-phenyl-1h-pyrazolo[3,4-c]pyridazin-5-yl)benzonitrile Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC(C#N)=C1 TXXVFAPDJYIMHK-UHFFFAOYSA-N 0.000 claims 1
• SNSHBMAWEIOBBA-UHFFFAOYSA-N 3-(3-amino-5-phenyl-1h-pyrazolo[3,4-c]pyridazin-4-yl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 SNSHBMAWEIOBBA-UHFFFAOYSA-N 0.000 claims 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims 1
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims 1
• YEWCUDXJAZHYNA-UHFFFAOYSA-N 3-[3-amino-4-(3-cyanophenyl)-1h-pyrazolo[3,4-c]pyridazin-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=C(C=CC=2)C#N)=C1 YEWCUDXJAZHYNA-UHFFFAOYSA-N 0.000 claims 1
• GIJRWUZFJIRXAR-UHFFFAOYSA-N 3-[3-amino-4-(4-chlorophenyl)-1h-pyrazolo[3,4-c]pyridazin-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=CC(Cl)=CC=2)=C1 GIJRWUZFJIRXAR-UHFFFAOYSA-N 0.000 claims 1
• LWKQFJPFSNGWFV-UHFFFAOYSA-N 3-[3-amino-5-(1,3-benzodioxol-5-yl)-1h-pyrazolo[3,4-c]pyridazin-4-yl]benzonitrile Chemical compound C=12C(N)=NNC2=NN=C(C=2C=C3OCOC3=CC=2)C=1C1=CC=CC(C#N)=C1 LWKQFJPFSNGWFV-UHFFFAOYSA-N 0.000 claims 1
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• ZKJXDBAZVHYAMJ-UHFFFAOYSA-N 4-phenyl-5-pyridin-2-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=N1 ZKJXDBAZVHYAMJ-UHFFFAOYSA-N 0.000 claims 1
• IFANCIKCINGFML-UHFFFAOYSA-N 4-phenyl-5-pyridin-3-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CN=C1 IFANCIKCINGFML-UHFFFAOYSA-N 0.000 claims 1
• RICMVBRPWQRDOI-UHFFFAOYSA-N 4-phenyl-5-thiophen-2-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CS1 RICMVBRPWQRDOI-UHFFFAOYSA-N 0.000 claims 1
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• OVAGBTYPAGXINN-UHFFFAOYSA-N 5-(2-chlorophenyl)-4-pyridin-3-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CN=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1Cl OVAGBTYPAGXINN-UHFFFAOYSA-N 0.000 claims 1
• YRXVOXOMKHQVSF-UHFFFAOYSA-N 5-(2-chlorophenyl)-4-pyridin-4-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=NC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1Cl YRXVOXOMKHQVSF-UHFFFAOYSA-N 0.000 claims 1
• OZYJUCYUGKRUAK-UHFFFAOYSA-N 5-(3-chlorophenyl)-4-(2-methylphenyl)-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound CC1=CC=CC=C1C1=C(C=2C=C(Cl)C=CC=2)N=NC2=C1C(N)=NN2 OZYJUCYUGKRUAK-UHFFFAOYSA-N 0.000 claims 1
• LSHSIQDFYHPADI-UHFFFAOYSA-N 5-(3-methoxyphenyl)-4-(3-nitrophenyl)-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound COC1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=C(C=CC=2)[N+]([O-])=O)=C1 LSHSIQDFYHPADI-UHFFFAOYSA-N 0.000 claims 1
• IONQCZAIDZHHME-UHFFFAOYSA-N 5-(3-methoxyphenyl)-4-pyridin-3-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound COC1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=NC=CC=2)=C1 IONQCZAIDZHHME-UHFFFAOYSA-N 0.000 claims 1
• OQEWMTRXRDPPTE-UHFFFAOYSA-N 5-(3-methoxyphenyl)-4-pyridin-4-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound COC1=CC=CC(C=2C(=C3C(N)=NNC3=NN=2)C=2C=CN=CC=2)=C1 OQEWMTRXRDPPTE-UHFFFAOYSA-N 0.000 claims 1
• KOMGFKVGLCEPAA-UHFFFAOYSA-N 5-(4-methylphenyl)-4-(3-nitrophenyl)-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C1=CC(C)=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=CC([N+]([O-])=O)=C1 KOMGFKVGLCEPAA-UHFFFAOYSA-N 0.000 claims 1
• WEPOYBFBJQJFSP-UHFFFAOYSA-N 5-(4-methylphenyl)-4-pyridin-3-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C1=CC(C)=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=CN=C1 WEPOYBFBJQJFSP-UHFFFAOYSA-N 0.000 claims 1
• LOOHNRBNAKCSME-UHFFFAOYSA-N 5-(4-methylphenyl)-4-pyridin-4-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C1=CC(C)=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=NC=C1 LOOHNRBNAKCSME-UHFFFAOYSA-N 0.000 claims 1
• JOHHRARENYRKKG-UHFFFAOYSA-N 5-(4-tert-butylphenyl)-4-phenyl-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NN=C(NN=C2N)C2=C1C1=CC=CC=C1 JOHHRARENYRKKG-UHFFFAOYSA-N 0.000 claims 1
• VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 claims 1
• XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 claims 1
• SIWYSLBKDCMCTI-UHFFFAOYSA-N 5-naphthalen-1-yl-4-phenyl-2h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=12C(N)=NNC2=NN=C(C=2C3=CC=CC=C3C=CC=2)C=1C1=CC=CC=C1 SIWYSLBKDCMCTI-UHFFFAOYSA-N 0.000 claims 1
• OQJKZGGGSJDJQX-UHFFFAOYSA-N 5-phenyl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C2=C(N)NN=C2N=NC=1C1=CC=CC=C1 OQJKZGGGSJDJQX-UHFFFAOYSA-N 0.000 claims 1
• RVLITJSYPGBNAJ-UHFFFAOYSA-N 5-phenyl-4-pyridin-2-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CC=NC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 RVLITJSYPGBNAJ-UHFFFAOYSA-N 0.000 claims 1
• CPNYORGACCVVMF-UHFFFAOYSA-N 5-phenyl-4-pyridin-3-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=CN=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 CPNYORGACCVVMF-UHFFFAOYSA-N 0.000 claims 1
• AAYSYKFZALTLMB-UHFFFAOYSA-N 5-phenyl-4-pyridin-4-yl-1h-pyrazolo[3,4-c]pyridazin-3-amine Chemical compound C=1C=NC=CC=1C1=C2C(N)=NNC2=NN=C1C1=CC=CC=C1 AAYSYKFZALTLMB-UHFFFAOYSA-N 0.000 claims 1
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